This MHCRC will have as its major emphasis the study of schizophrenia and its related spectrum disorders. Its unifying concept will be the goal of linking the clinical picture of the illness with its underlying neurobiology. This CRC will be composed of seven research units. These units will conduct the integrative and interdisciplinary research that is needed to advance our knowledge concerning the clinical presentation of schizophrenia and its relation to pathophysiology, etiology, prevention, and treatment. The DIAGNOSIS AND PHENOMENOLOGY UNIT will examine clinical issues, including evaluation, nosology, longitudinal outcome, and instrument development. The BRAIN IMAGING UNIT will focus on structural and functional brain abnormalities, using CT scanning, MRI, SPECT, and PET; these studies will attempt to integrate our understanding of the clinical symptoms, such as hallucinations, with the neural mechanisms that underlie them. The GENETICS UNIT will take a comprehensive approach to the genetics of schizophrenia, using multiplex family studies, twin studies, adoption studies, and molecular genetics. Multiple biological measures will also be obtained in order to attempt to identify markers. The NEUROENDOCRINOLOGY UNIT will examine cortical-hypothalamic-pituitary-target organ axes in the major psychoses. The EPIDEMIOLOGY UNIT will explore mortality in schizophrenia, birth injury, and other risk factors; this unit will work closely with the GENETICS UNIT in order to examine the environmental side of the genetic versus environmental interaction. The BASIC NEUROBIOLOGY UNIT will conduct research on animal models of psychosis, with particular emphasis on neurochemical systems. The NEUROPHARMACOLOGY UNIT will pursue the study of pharmacokinetics, drug dosage, target symptoms, and side effects. Three CORE UNITS will support these research units: ADMINISTRATIVE, ASSESSMENT AND TRAINING, and BIOSTATISTICS. This MHCRC will build on existing resources at Iowa, such as an excellent clinical population, a strong research tradition, and established collaborative relationships with Radiology, Internal Medicine, Preventive Medicine, and Pharmacology. In addition, we will continue to place a major emphasis on the training of young investigators in research careers in schizophrenia.